Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

BioMed Central full text link BioMed Central Free PMC article
Full text links

Actions

Share

.2018 Sep 4;19(1):157.
doi: 10.1186/s12881-018-0630-9.

Clinical and molecular characterization of POU3F4 mutations in multiple DFNX2 Chinese families

Affiliations

Clinical and molecular characterization of POU3F4 mutations in multiple DFNX2 Chinese families

Yu Su et al. BMC Med Genet..

Abstract

Background: Many X-linked non-syndromic hearing loss (HL) cases are caused by various mutations in the POU domain class 3 transcription factor 4 (POU3F4) gene. This study aimed to identify allelic variants of this gene in two Chinese families displaying X-linked inheritance deafness-2 (DFNX2) and one sporadic case with indefinite inheritance pattern.

Methods: Direct DNA sequencing of the POU3F4 gene was performed in these families and in 100 Chinese individuals with normal hearing.

Results: There are characteristic imaging findings in DFNX2 Chinese families with POU3F4 mutations. The temporal bone computed tomography (CT) images of patients with DFNX2 are characterized by a thickened stapes footplate, hypoplasia of the cochlear base, absence of the bony modiolus, and dilated internal acoustic meatus (IAM) as well as by abnormally wide communication between the IAM and the basal turn of the cochlea. We identified three causative mutations in POU3F4 for three probands and their extended families. In family 1468, we observed a novel deletion mutation, c.973delT, which is predicted to result in a p.Trp325Gly amino acid frameshift. In family 2741, the mutation c.927delCTC was identified, which is predicted to result in the deletion of serine at position 310. In both families, the mutations were located in the POU homeodomain and are predicted to truncate the C-terminus of the POU domain. In the third family, a novel de novo transversion mutation (c.669 T > A) was identified in a 5-year-old boy that resulted in a nonsense mutation (p.Tyr223*). The mutation created a new stop codon and is predicted to result in a truncated POU3F4 protein.

Conclusions: Based on characteristic radiological findings and clinical features, POU3F4 gene mutation analysis will increase the success rate of stapes operations and cochlear implantations, and improve molecular diagnosis, genetic counseling, and knowledge of the molecular epidemiology of HL among patients with DFNX2.

Keywords: DFNX2; Mutation; POU3F4; X-linked deafness.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Chinese PLA General Hospital Research Ethics Committee.

Consent for publication

Fully informed written consent for participation and publication of the clinical data was obtained from each subject or from the guardians of subjects < 18 years old.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Pedigree, clinical phenotypes, and mutation analysis in family 1486.a Temporal bone computed tomography (CT) images of the proband of family 1486 demonstrating dilation of the lateral end of the internal acoustic meatus (IAM) and a malformed cochlea; the basal turn of the cochlea was incompletely separated from the IAM (arrow);b Pedigree of Family 1486 with multiple congenital profound sensorineural hearing impairment cases (Affected subjects are denoted in black. Arrow indicates the proband. Mutation carrier are denoted with dot within a symbol);c Wild-type sequence ofPOU3F4 including sites 927–929;d A heterozygous c.927delCTC mutation was found in the female carriers;e A hemizygotic c.927delCTC mutation was detected in the affected males;f Amino acid changes caused by changes in the DNA sequence. A three-nucleotide deletion (from position 927 to 929) in the coding region ofPOU3F4 results in the deletion of serine at position 310
Fig. 2
Fig. 2
Pedigree, clinical phenotypes and mutation analysis in family 2741.a Pedigree of family 2741 with congenital mixed hearing impairment and sensorineural hearing impairment cases (Affected subjects are denoted in black. Arrow indicates the proband. Mutation carrier are denoted with dot within a symbol);b Audiograms of both ears for the proband, who exhibited typical audiometric features of mixed hearing impairment;c Temporal bone CT images of the proband demonstrating dilation of the bottom of the IAM and a deficit in the bony plate, which separates the basal turn of the cochlea and the IAM (arrow);d Audiograms of both ears from the uncle of the proband, who shows profound sensorineural hearing impairment;e Temporal bone CT images of the uncle of the proband demonstrating dilation of the lateral end of the IAM and bone deficiency between the basal turn of the cochlea and the IAM (arrow).f Wild-type sequence ofPOU3F4 including position 973;g A heterozygous c.973delT mutation was found in the female carriers;h A hemizygotic c.973delT mutation was detected in the affected males;i Amino acid change caused by changes in the DNA sequence leading to a predicted frameshift mutation and truncation of the POU3F4 protein;j Panel 1 marks the position of the c.973delT (p.Trp325Glyfs*12) mutation and panel 2 marks the position of the c.927delCTC (p.Ser310del) mutation. The POU homeodomain (from Gly276 to Arg335) is highly conserved in different species
Fig. 3
Fig. 3
Pedigree, clinical phenotypes and mutation analysis in family ZSJ.a Audiograms of both ears from the proband exhibited profound sensorineural hearing impairment;b Temporal bone CT images of the proband demonstrating dilation of the lateral end of the IAM and a deficit in the basal turn of the cochlea in the right ear (arrow) in addition to dilation of the lateral end of the IAM and an incompletely developed cochlea in the left ear (arrow);c Wild-type sequence ofPOU3F4, including site 669;d A hemizygotic c.669 T > A mutation was detected in the affected boy;e Pedigree of family ZSJ;f Stop codon caused by changes in the DNA sequence;g Molecular modeling of wild-type and mutant POU3F4 proteins. The c.669 T > A mutant creates a new stop codon and is predicted to result in a truncated protein lacking normal POU3F4 transcription factor function
Fig. 4
Fig. 4
Schematic illustration of the POU3F4 protein. In this study, three mutations were identified: the p.Tyr223*mutation located in the POU-specific domain, and the p.Trp325Glyfs*12 and p.Ser310del mutations located in the POU homeodomain
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Morton CC, Nance WE. Newborn hearing screening--a silent revolution. N Engl J Med. 2006;354(20):2151–2164. doi: 10.1056/NEJMra050700. - DOI - PubMed
    1. Marazita ML, et al. Genetic epidemiological studies of early-onset deafness in the U.S. school-age population. Am J Med Genet. 1993;46(5):486–491. doi: 10.1002/ajmg.1320460504. - DOI - PubMed
    1. Morton NE. Genetic epidemiology of hearing impairment. Ann N Y Acad Sci. 1991;630:16–31. doi: 10.1111/j.1749-6632.1991.tb19572.x. - DOI - PubMed
    1. Liu X, et al. Loss-of-function mutations in the PRPS1 gene cause a type of nonsyndromic X-linked sensorineural deafness, DFN2. Am J Hum Genet. 2010;86(1):65–71. doi: 10.1016/j.ajhg.2009.11.015. - DOI - PMC - PubMed
    1. de Kok YJ, et al. Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4. Science. 1995;267(5198):685–688. doi: 10.1126/science.7839145. - DOI - PubMed

Publication types

MeSH terms

Substances

Supplementary concepts

Related information

LinkOut - more resources

Full text links
BioMed Central full text link BioMed Central Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp